Methylphenidate is a chiral molecule. The properties of the enantiomers have been investigated to some extent, although the drug is still administered as the racemate. It is generally thought that d-threo-methylphenidate is the active metabolite.
Methylphenidate is a known drug and controlled substance used primarily to treat hyperactive children. Attention Deficit Disorder (ADD) and Attention Deficit/Hyperactivity Disorder (ADHD) (severally and collectively hereinafter referred to as “ADD”) are developmental disorders of self-control. They consist of problems with attention span, impulse control and activity level. These problems are reflected in impairment of a person's will or capacity to control his or her own behavior relative to the passage of time and to keep future goals and consequences in mind.
Traditionally, methylphenidate has been used as a drug of choice for the treatment of ADD in both children and adults for several reasons. Methylphenidate, described in U.S. Pat. No. 2,957,880, is a central nervous system stimulant. Though not an amphetamine, methylphenidate functions in the brain in a way similar to amphetamines. Current commercially available dosage forms containing methylphenidate are marketed under the names Ritalin® and Concerta® tablets.
U.S. Pat. Nos. 6,919,337 and 6,930,129 to Alza Corporation teach a dosage form and a method of administering methylphenidate in a controlled release formulation providing an ascending release rate. The dosage form disclosed in the '337 and '129 patents comprises a layered tablet core including an expanding “push layer” which serves to facilitate release of the active ingredient contained within the tablet.
International patent application, PCT Publication No. WO 97/03672 (Chiroscience Ltd.), discloses that methyiphenidate exhibits a therapeutic effect when administered in the form of a racemic mixture or in the form of a single isomer (such as the RR d-threo enantiomer). Further, WO 97/03763 (Chiroscience Ltd.) discloses a sustained release formulation containing the d-threo-methylphenidate (dtmp) enantiomer. This disclosure teaches the use of a composition comprising a coating through which the dtmp passes in order to attain sustained release and achieve serum levels (of the active ingredient) of at least 50% Cmax over a period of at least 8 hours.
There is an unmet commercial need for a formulation which can provide controlled or sustained release dosage form containing methylphenidate which can be manufactured using a conventional pharmaceutical manufacturing process that can be advantageous to consumers and insurers.